Rapid development of a vaccine to prevent the global health crisis is a global imperative, and defining the stakes and potential hurdles is critical because regulatory and medical decisions are based on benefit/risk calculations. The benefit of developing an effective covid-19 vaccine is very high, and even greater if it can be deployed in time to prevent repeated or continuous epidemics. A recent article in the New England Journal of Medicine said that the need to rapidly develop a covid-19 vaccine comes at a time of explosion in basic scientific understanding, including in areas such as genomics and structural biology, that is supporting a new era in vaccine development. “Over the past decade, the scientific community and the vaccine industry have been asked to respond urgently to epidemics of H1N1 influenza, Ebola, Zika, and now SARS-CoV-2. An H1N1 influenza vaccine was developed relatively rapidly, largely because influenza-vaccine technology was well developed and key regulators had previously decided that vaccines made using egg- and cell-based platforms could be licensed under the rules used for a strain change. Although a monovalent H1N1 vaccine was not available before the pandemic peaked in the Northern Hemisphere, it was available soon afterward as a stand-alone vaccine and was ultimately incorporated into commercially available seasonal influenza vaccines,” the authors wrote.
The article goes on to say that multiple platforms are under development. Active biotech companies with recent developments include Hoth Therapeutics, Inc., Gilead Sciences, Inc., Inovio Pharmaceuticals, Inc., Sorrento Therapeutics, Inc., and Vaxart, Inc.
Among those with the greatest potential for speed are DNA- and RNA-based platforms, followed by those for developing recombinant- subunit vaccines. RNA and DNA vaccines can be made quickly because they require no culture or fermentation, instead using synthetic processes. Developers’ and regulators’ experience with these platforms for personal oncology vaccines can facilitate rapid testing and release. There are no approved RNA vaccines to date, but RNA vaccines have entered clinical trials, and regulators have experience in reviewing clinical trial applications and with associated manufacturing of the vaccines.
“Hoth has assembled a unique and portfolio of therapeutics, that is each addressing significant unmet market needs globally,” stated Robb Knie, CEO of Hoth Therapeutics. “We have partnered with some of the most renowned doctors, clinics, and scientific institutions as we strive to bring these innovative therapeutic solutions through the clinic. We have several significant milestones upcoming throughout the rest of 2020 into next year including our human study for BioLexa, targeting the treatment of eczema in adolescents. Management remains committed to developing, and bringing these novel treatments to market and improving the lives of those that require them.”
VaxCelerate (COVID-19) – VaxCelerate is self-assembling vaccine (SAV) platform designed to protect patients at risk of Coronavirus (COVID-19) infection. VaxCelerate is believed to offer unique advantages over other compounds in combination therapy. In infectious applications, it allows rapid development against viruses and other pathogens. The vaccine focuses on both DNA and internal / external mutated proteins providing the immune system with more potential targets to attack. VaxCelerate is currently in animal trials and will share those results as the testing completes.
Novel Peptide Therapeutic (COVID-19) – The Company recently licensed technology and intellectual property exclusively from Virginia Commonwealth University for a novel peptide therapeutic to prevent spike protein binding, a potential leading cause of COVID-19. This treatment could be a breakthrough in slowing the transmission of the virus. Current research is being led by inventor, Michael H. Peters, Ph.D., Professor, Department of Chemical and Life Science Engineering at VCU, College of Engineering. The work is being aided, in part, by powerful supercomputers as part of the COVID-19 High Performance Computing Consortium through a virtual system that scientists can use to interactively share computing resources known as the Extreme Science and Engineering Discovery Environment. Hoth hopes to have an update as to further collaboration with VCU in the month ahead.
The company recently announced topline results from the Phase 3 SIMPLE trial in hospitalised patients with moderate COVID-19 pneumonia. This open-label study evaluated 5-day and 10-day courses of the investigational antiviral remdesivir plus standard of care, versus standard of care alone. The study demonstrated that patients in the 5-day remdesivir treatment group were 65 percent more likely to have clinical improvement at Day 11 compared with those in the standard of care group (OR 1.65 [95% CI 1.09-2.48]; p=0.017). The odds of improvement in clinical status with the 10-day treatment course of remdesivir versus standard of care were also favorable, trending toward but not reaching statistical significance (OR 1.31 [95% CI 0.88-1.95]; p=0.18). No new safety signals were identified with remdesivir across either treatment group. Gilead plans to submit the full data for publication in a peer-reviewed journal in the coming weeks.
“Our understanding of the spectrum of SARS-CoV-2 infection severity and presentations of COVID-19 continues to evolve,” said Francisco Marty, MD, an infectious diseases physician at Brigham and Women’s Hospital, and associate professor of medicine at Harvard Medical School. “These study results offer additional encouraging data for remdesivir, showing that if we can intervene earlier in the disease process with a 5-day treatment course, we can significantly improve clinical outcomes for these patients.”
This company recently announced the publication of the preclinical study data for IN0-4800, its COVID-19 DNA vaccine, demonstrating robust neutralizing antibody and T cell immune responses against coronavirus SARS-CoV-2. The study was published in the peer-reviewed journal Nature Communications titled, “Immunogenicity of a DNA vaccine candidate for COVID-19” by INOVIO scientists and collaborators from The Wistar Institute, the University of Texas, Public Health England, Fudan University, and Advaccine.
Dr. Kate Broderick, INOVIO’s Senior Vice President of R&D and the Team Lead for COVID-19 vaccine development, said, “These positive preclinical results from our COVID-19 DNA vaccine (INO-4800) not only highlight the potency of our DNA medicines platform, but also build on our previously reported positive Phase 1/2a data from our vaccine against the coronavirus that causes MERS, which demonstrated near-100% seroconversion and neutralization from a similarly designed vaccine INO-4700. The potent neutralizing antibody and T cell immune responses generated in multiple animal models are supportive of our currently on-going INO-4800 clinical trials.”
Sorrento recently announced that it has received clearance from the U.S. Food and Drug Administration (FDA) for its investigational new drug (IND) application for STI-6129, a CD38-targeting antibody drug conjugate (ADC). STI-6129 utilizes several technology platforms that are under development by Sorrento Therapeutics, including a CD38 specific antibody identified from its fully human G-MAB™ antibody library, its proprietary drug payload Duostatin 5 and its site-specific C-LOCK conjugation technology.
“That the FDA cleared our STI-6129 IND application to proceed to human trials is another important milestone for Sorrento,” stated Dr. Henry Ji, Chairman and CEO of Sorrento Therapeutics. “Together with our CD38 CAR-T program, this has the potential to provide additional therapeutic options for patients in need. We are looking forward to further evaluating the safety and efficacy of STI-6129 in clinical trials.”
This clinical-stage biotechnology company is developing oral recombinant vaccines that are administered by tablet rather than by injection. The company recently announced that it has selected its lead COVID-19 vaccine candidate and has contracted with KindredBio to manufacture bulk vaccine under cGMP to complement the manufacturing capacity of partner Emergent BioSolutions.
“All our COVID-19 vaccine constructs were highly immunogenic in preclinical testing, and we are taking the candidate forward that is expected to generate the broadest immune response in humans,” said Sean Tucker, Ph.D., chief scientific officer of Vaxart. “In a phase 2 efficacy study that was recently published in the Lancet Infectious Diseases, we have demonstrated that our oral H1 flu tablet vaccine protected against influenza infection after just one dose. Based on these results, we believe our vaccines are ideal to protect against mucosal respiratory viruses such as SARS-CoV-2, the virus that causes COVID-19.”
In January 2020, Vaxart initiated a program to develop a COVID-19 vaccine based on its VAAST oral vaccines platform. The Company evaluated multiple vaccine candidates in its preclinical models and has chosen the lead candidate for cGMP manufacturing and clinical testing based on the magnitude and the breadth of the immune response. Vaxart has contracted with Emergent BioSolutions and Kindred Biosciences, Inc. to produce bulk vaccine under cGMP for upcoming clinical trials. The vaccine tablets will be manufactured at Vaxart.